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Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Heart Failure With Preserved Ejection Fraction: A Systematic
Amir Saeed1,2, Bilal Younas3, Ali Rohan4
1Acute Medicine, Norfolk and Norwich University Hospital, Norwich, GBR.
Cureus
|July 22, 2025
Summary
Sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly reduce cardiovascular death and hospitalizations in patients with heart failure with preserved ejection fraction (HFpEF). These drugs also improve patient-reported symptoms and slow kidney disease progression.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Heart failure with preserved ejection fraction (HFpEF) presents challenges in ventricular filling and leads to frequent hospitalizations.
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors show promise for cardiovascular and renal benefits in heart failure populations.
- The specific impact of SGLT2 inhibitors on HFpEF outcomes requires further investigation.
Purpose of the Study:
- To systematically review the effects of SGLT2 inhibitors on clinical outcomes in patients with HFpEF.
- To evaluate impacts on cardiovascular death, heart failure hospitalizations, exercise capacity, symptoms, and kidney disease progression.
Main Methods:
- Systematic review of randomized controlled trials (RCTs) published between January 2015 and April 2025.
- Searched PubMed, Embase, and Cochrane Library for studies on empagliflozin, dapagliflozin, sotagliflozin, canagliflozin, and ertugliflozin in HFpEF.
- Assessed methodological quality using the Mixed Methods Appraisal Tool (MMAT); 10 studies were high quality (low risk of bias).
Main Results:
- SGLT2 inhibitors significantly reduced cardiovascular death and heart failure-related hospitalizations.
- Improvements were noted in patient-reported outcomes, specifically Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom scores.
- Significant renal benefits included reduced kidney disease progression and fewer cardiovascular-related renal outcomes.
Conclusions:
- SGLT2 inhibitors offer substantial cardiovascular and renal protective benefits for patients with HFpEF.
- These agents improve patient-reported symptoms and slow the progression of kidney disease.
- The findings support the use of SGLT2 inhibitors as a therapeutic option in managing HFpEF.
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